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OBJECTIVES: Chronic inflammation promotes cardiovascular risk in rheumatoid arthritis (RA). Biological disease-modifying antirheumatic drugs (bDMARDs) improve disease activity and cardiovascular disease outcomes. We explored whether bDMARDs influence the impact of disease activity and inflammatory markers on long-term cardiovascular risk in RA. METHODS: We studied 4370 participants without cardiovascular disease in a 10-country observational cohort of patients with RA. Endpoints were (1) major adverse cardiovascular events (MACE) encompassing myocardial infarction, stroke and cardiovascular death; and (2) any ischaemic cardiovascular events (iCVE) including MACE plus revascularisation, angina, transient ischaemic attack and peripheral arterial disease. RESULTS: Over 26 534 patient-years, 239 MACE and 362 iCVE occurred. The interaction between 28-joint Disease Activity Score with C-reactive protein (DAS28-CRP) and bDMARD use was significant for MACE (p=0.017), suggesting the effect of DAS28-CRP on MACE risk differed among bDMARD users (n=515) and non-users (n=3855). DAS28-CRP (per unit increase) is associated with MACE risk in bDMARD non-users (HR 1.21 (95% CI 1.07 to 1.37)) but not users (HR 0.69 (95% CI 0.40 to 1.20)). The interaction between CRP (per log unit increase) and bDMARD use was also significant for MACE (p=0.011). CRP associated with MACE risk in bDMARD non-users (HR 1.16 (95% CI 1.04 to 1.30)), but not users (HR 0.65 (95% CI 0.36 to 1.17)). No interaction was observed between bDMARD use and DAS28-CRP (p=0.167) or CRP (p=0.237) for iCVE risk. CONCLUSIONS: RA activity and inflammatory markers associated with risk of MACE in bDMARD non-users but not users suggesting the possibility of biological-specific benefits locally on arterial wall independently of effects on systemic inflammation.

ObjectiveAccurate identification of lupus nephritis (LN) cases is essential for patient management, research and public health initiatives. However, LN diagnosis codes in electronic health records (EHRs) are underused, hindering efficient identification. We investigated the current performance of International Classification of Diseases (ICD) codes, 9th and 10th editions (ICD9/10), for identifying prevalent LN, and developed scoring systems to increase identification of LN that are adaptable to settings with and without LN ICD codes.MethodsTraining and test sets derived from EHR data from a large health system. An external set comprised data from the EHR of a second large health system. Adults with ICD9/10 codes for SLE were included. LN cases were ascertained through manual chart reviews conducted by rheumatologists. Two definitions of LN were used: strict (definite LN) and inclusive (definite, potential or diagnostic uncertainty). Gradient boosting models including structured EHR fields were used for predictor selection. Two logistic regression-based scoring systems were developed ('LN-Code' included LN ICD codes and 'LN-No Code' did not), calibrated and validated using standard performance metrics.ResultsA total of 4152 patients from University of California San Francisco Medical Center and 370 patients from Zuckerberg San Francisco General Hospital and Trauma Center met the eligibility criteria. Mean age was 50 years, 87% were female. LN diagnosis codes demonstrated low sensitivity (43-73%) but high specificity (92-97%). LN-Code achieved an area under the curve (AUC) of 0.93 and a sensitivity of 0.88 for identifying LN using the inclusive definition. LN-No Code reached an AUC of 0.91 and a sensitivity of 0.95 (0.97 for the strict definition). Both scoring systems had good external validity, calibration and performance across racial and ethnic groups.ConclusionsThis study quantified the underutilisation of LN diagnosis codes in EHRs and introduced two adaptable scoring systems to enhance LN identification. Further validation in diverse healthcare settings is essential to ensure their broader applicability.

BackgroundThere is little robust data about the cardiovascular safety of hydroxychloroquine in patients with rheumatoid arthritis (RA), who often have cardiovascular comorbidities. We examined the association between use of hydroxychloroquine (HCQ) in patients with RA and major adverse cardiovascular events (MACE).MethodsIn a retrospective cohort of Medicare beneficiaries aged ≥ 65 years with RA, we identified patients who initiated HCQ (users) and who did not initiate HCQ (non-users) between January 2015-June 2017. Each HCQ user was matched to 2 non-users of HCQ using propensity score derived from patient baseline characteristics. The primary outcome was the occurrence of MACE, defined as acute admissions for stroke, myocardial infarction, or heart failure. Secondary outcomes included all-cause mortality and the composite of MACE and all-cause mortality. Cox proportional hazards model was used to compare outcomes between HCQ users to non-users.ResultsThe study included 2380 RA patients with incident HCQ use and matched 4633 HCQ non-users over the study period. The mean follow-up duration was 1.67 and 1.63 years in HCQ non-users and users, respectively. In multivariable models, use of HCQ was not associated with the risk of MACE (hazard ratio 1.1; 95% CI: 0.832-1.33). However, use of HCQ was associated with a lower risk of all-cause mortality (HR: 0.54; 95% CI: 0.45-0.64) and the composite of all-cause mortality and MACE (HR 0.67; 95% CI: 0.58-0.78).ConclusionHCQ use was independently associated with a lower risk of mortality in older adults with RA but not with incidence of MACE events. Key Points • Using an incident user design (to avoid the biases of a prevalent user design) and a population-based approach, we examined the effect of hydroxychloroquine (HCQ) on the risk of major cardiovascular events (MACE) in older patients with RA. • We did not find an association between HCQ use and incident MACE. We did, however, find a significant association with the composite outcome (MACE and all-cause mortality) driven by a significant reduction in all-cause mortality with HCQ use.

Objectives To investigate the predictive factors for difficult-to-treat rheumatoid arthritis (D2T RA) and assess the efficacy of biologic DMARDs (bDMARDs) and Janus kinase inhibitors (JAKi). Methods Retrospective analysis was conducted on data from the ANSWER cohort comprising 3623 RA patients treated with bDMARDs or JAKi in Japan. Multivariate Cox proportional hazards modelling was used to analyse the hazard ratios (HRs) for treatment retention. Results Of the 3623 RA patients, 450 (12.4%) met the first two criteria of the EULAR D2T RA definition (defined as D2T RA in this study). Factors contributing to D2T RA included age over 75 (compared with those under 65, hazard ratio [HR] = 0.46; 95% CI: 0.31, 0.69), higher rheumatoid factor (RF) titres (HR = 1.005; 95% CI: 1.00, 1.01), higher clinical disease activity index (HR = 1.02; 95% CI: 1.01, 1.03), lower methotrexate dosage (HR = 0.97; 95% CI: 0.95, 0.99), and comorbidities like hypertension (HR = 1.53; 95% CI: 1.2, 1.95) and diabetes (HR = 1.37; 95% CI: 1.09, 1.73). Anti-IL-6 receptor antibodies (aIL-6R, HR = 0.53; 95% CI: 0.37, 0.75) and JAKi (HR = 0.64; 95% CI: 0.46, 0.90) were associated with fewer discontinuations due to ineffectiveness compared with TNF inhibitors. Oral glucocorticoid usage (HR = 1.65; 95% CI: 1.11, 2.47) was linked to increased discontinuation due to toxic adverse events. Conclusion Younger onset, higher RF titres, and comorbidities predicted D2T RA development. For managing D2T RA, aIL-6R and JAKi exhibited superior drug retention. [ABSTRACT FROM AUTHOR]

Objective To present the characteristics of patients with potential difficult-to-treat (D2T) PsA. Methods We used data from the Greek multicentre registry of PsA patients. D2T PsA was defined as follows: patients with at least 6 months' disease duration, who have failed to at least one conventional synthetic DMARD and at least two biologic DMARDs/targeted synthetic DMARDs with a different mechanism of action and have either at least moderate disease activity (MODA) defined as DAPSA (Disease Activity index in PSoriatic Arthritis) >14, and/or are not at minimal disease activity (MDA). Demographic and clinical characteristics were compared between D2T and non-D2T PsA patients. In two sensitivity analyses, patients classified as D2T solely according to the MODA or MDA criterion were examined separately. Results Among 467 patients included, 77 (16.5%) were considered D2T and 390 non-D2T PsA. Compared with non-D2T, patients with D2T PsA presented more commonly with extensive psoriasis (P  < 0.0001) and were more likely to have higher BMI (P  = 0.023) and a history of IBD (P  = 0.026). In the MODA and MDA sensitivity analyses, 7.5% and 12.5% of patients were considered D2T, respectively. In both sensitivity analyses, extensive psoriasis was again identified as an independent variable for D2T PsA (P  = 0.001 and P  = 0.008, respectively). Moreover, female gender (P  = 0.034) in the MODA analysis and axial disease (P  = 0.040) in the MDA analysis were independent variables for D2T PsA. Conclusion Despite the availability of therapies, D2T PsA is common in real-life cohorts of patients with PsA and extensive psoriasis. High BMI, female gender, axial disease and history of IBD were also associated with D2T PsA. [ABSTRACT FROM AUTHOR]

Objectives To explore differences in axial spondyloarthritis (axSpA) clinical phenotype around the world in a large sample of patients included in the International Map of Axial Spondyloarthritis (IMAS). Method IMAS was a cross-sectional online survey (2017–2022) of 5557 unselected axSpA patients from 27 countries. We analysed across five geographic regions the age at symptom onset, diagnostic delay, gender, HLA-B27, family history, extra-musculoskeletal manifestations, presence of comorbidities, disease activity (BASDAI), level of spinal stiffness and treatments. Results Of 5557 IMAS participants, 3493 were from Europe, 770 from North America, 600 from Asia, 548 from Latin America and 146 from South Africa. Age at symptom onset ranged between 25 and 30 years and was higher in Latin America. Diagnostic delay was longest in South Africa and lowest in Asia. The lowest HLA-B27 positivity was observed in Latin America and the highest in Asia. Extra-musculoskeletal manifestations were the lowest in Europe. Mean disease activity (BASDAI) was 5.4, with highest values in South Africa and lowest in Asia. Most of the patients had used NSAIDs for their condition and less than half had ever taken conventional synthetic DMARDS; both were more frequent in Latin America and South Africa. Almost half of the patients had ever taken biologic DMARDs, more frequent use being in the Americas. Conclusion There is great heterogeneity of axSpA clinical phenotype presentation around the world. AxSpA manifests differently in different regions, so further understanding of these differences of phenotypes is needed to achieve early diagnosis and initiation of optimal disease treatment in axSpA in the different regions. [ABSTRACT FROM AUTHOR]

Objectives: This post hoc analysis of the RAJ2 study assessed long-term safety and effectiveness of peficitinib 100 mg/day for treatment of rheumatoid arthritis. Methods: Eligible patients previously completed two Phase 3 (RAJ3 and RAJ4) studies of peficitinib in Asia. All patients received peficitinib 100 mg/day at RAJ2 Week (W)0; dose change to 50 mg/day or 150 mg/day was permitted. Safety endpoints included treatment-emergent adverse events and laboratory test results. Effectiveness endpoints included peficitinib exposure pattern, achievement of Clinical Disease Activity Index (CDAI) remission by peficitinib exposure pattern at W0 and W48, and association of demographics/characteristics with CDAI remission at W0 and W48. Results: Overall, no new safety findings were reported at W48, and renal function was unaffected. Of patients included in effectiveness analyses at W48, 70.9% (451/636) had maintained peficitinib 100 mg/day since W0. Of patients who achieved CDAI remission at W0 and maintained peficitinib 100 mg/day to W48, 50.3% (79/157) maintained CDAI remission to W48. Low disease activity and a lower number of prior disease-modifying antirheumatic drugs were significantly associated with CDAI remission at W48. Conclusions: Long-term peficitinib treatment at a dose of 100 mg/day was generally well tolerated and, following induction therapy, maintained effectiveness through to W48. [ABSTRACT FROM AUTHOR]

Objective: To compare healthcare resource utilisation (HCRU) and direct costs between responders versus non-responders to advanced therapies for rheumatoid arthritis (RA). Methods: Patients initiating ≥1 advanced therapy (October 2018 − September 2019) with ≥1 RA claim (6-month pre-index period), ≥2 RA claims (any period), and ≥12 months follow-up were identified from the Medical Data Vision claims database. HCRU and all-cause and RA-related costs [direct medical, emergency department (ED), laboratory, and pharmacy] were compared between responders and non-responders. Adjusted incidence rate ratios (IRRs) for HCRU or cost were calculated via multivariable analyses. Results: Among 2446 patients [non-responders (n = 1817); responders (n = 629)], non-responders had significantly longer hospitalisation days [IRR: 1.8 (95% CI: 1.2 − 2.6)], and significantly more ED visits [2.5 (1.5 − 4.2)] and prescriptions [1.1 (1.1 − 1.2)]. Mean all-cause hospital/outpatient medical costs were significantly higher for non-responders [1.4 (1.3 − 1.6), ¥530,895 versus ¥357,009 ($3992 versus $2684) for responders; ¥173,886 ($1307) difference]; RA-related medical costs showed a similar trend [¥351,306 vs ¥253,030 ($2641 vs $1902); ¥98,276 ($739) difference]. No differences between responders and non-responders were observed in mean all-cause and RA-related pharmacy costs. Conclusions: Non-responders to advanced therapies had greater HCRU and all-cause/RA-related direct costs as compared with responders, suggesting a need for more effective RA therapies to reduce the economic burden associated with non-response. [ABSTRACT FROM AUTHOR]

Objectives: We evaluated the medication selection and clinical characteristics of rheumatoid arthritis patients who started treatment with/without methotrexate (MTX) (using biologic disease-modifying antirheumatic drugs or Janus kinase inhibitors instead) in Japan. Methods: Using a Japanese hospital-based administrative claims database, rheumatoid arthritis patients who received treatment [abatacept (ABA), interleukin-6 receptor inhibitor, tumor necrosis factor inhibitor, or Janus kinase inhibitor] between 1 January 2015 and 31 December 2019 were enrolled. Results: Overall, 19,301 patients were included (10,530 receiving MTX; 8771 not receiving MTX within 60 days of the first treatment). Mean ages at diagnosis were 60.7 and 65.9 years in the MTX and non-MTX groups, respectively (P < .0001). The non-MTX group had higher proportions of patients with Charlson Comorbidity Index ≥1 (P < .0001) and higher comorbidity rates. ABA was the most frequently used drug among patients with infectious/parasitic, circulatory, and respiratory diseases at baseline. Interleukin-6 receptor inhibitor had the highest use rate among patients with neoplasms; blood, gastrointestinal, and genitourinary diseases; and abnormal clinical/laboratory findings. ABA had the highest persistence probability from 6 months onward. Conclusions: MTX is used less frequently among older Japanese rheumatoid arthritis patients or those with comorbidities. In such patients, ABA is the most frequently used drug, followed by interleukin-6 receptor inhibitor, when MTX is not used at treatment start. [ABSTRACT FROM AUTHOR]

Objectives: Our objective was to investigate trends in the treatment of patients with late-onset rheumatoid arthritis (LORA) using data from the National Database of Rheumatic Diseases in Japan (NinJa). Methods: Patients registered in the National Database of Rheumatic Diseases in Japan were classified according to the disease onset: at <65 years (young-onset rheumatoid arthritis); at 65–74 years (early LORA); and at ≥75 years (late LORA). Chronological changes in the treatment and disease activity were compared. Results: A total of 7178, 13,171, 15,295, and 15,943 patients were evaluated in 2010, 2013, 2016, and 2019, respectively. In all groups, the use of methotrexate gradually decreased, whereas that of biological/targeted synthetic disease-modifying antirheumatic drugs (DMARDs) increased; the use of tumor necrosis factor inhibitors decreased, whereas that of non-tumor necrosis factor inhibitors increased. LORA was characterized by more single DMARD use and less methotrexate and biological/targeted synthetic DMARD use. Tumor necrosis factor inhibitors and interleukin-6 inhibitors were used less frequently, whereas abatacept was utilized more frequently in late versus early LORA. Conventional synthetic DMARD (excluding methotrexate) and glucocorticoid use was higher in late versus early LORA. Conclusions: This analysis revealed chronological changes in the treatment of LORA in Japan. Differences between early and late LORA suggest that patients are not a homogeneous population. [ABSTRACT FROM AUTHOR]

Objectives: To update an evidence base informing the 2024 Japan College of Rheumatology clinical practice guidelines for the management of rheumatoid arthritis (RA) in older adults. Methods: Four clinical questions (CQs) regarding efficacy and safety of drug treatment were evaluated, with CQ1 addressing methotrexate (MTX), CQ2 biological disease-modifying antirheumatic drugs, CQ3 Janus kinase (JAK) inhibitors, and CQ4 glucocorticoids (GCs). Quality of the evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation system. Results: Observational studies confirmed a pivotal role of methotrexate in the treatment of older RA patients. The meta-analysis showed that tumour necrosis factor inhibitors and JAK inhibitors were unequivocally effective in older RA patients. No data indicated that biological disease-modifying antirheumatic drugs were unsafe for older patients. No safety data for JAK inhibitor use in older patients were available. One randomized controlled trial demonstrated that long-term treatment with low-dose GCs increased risks of GC-associated adverse events. The certainty of overall evidence was very low for all CQs. Conclusions: This systematic review provides the necessary evidence for developing 2024 Japan College of Rheumatology clinical practice guidelines for managing older patients with RA. Continued updates on the evidence of JAK inhibitors and GC are desired. [ABSTRACT FROM AUTHOR]

Objectives: Our study aimed to evaluate the relationship of small joint involvement with demographic, clinical, and laboratory findings and to determine its possible effects on prognosis. Methods: This retrospective observational study was conducted in patients diagnosed with oligoarticular juvenile idiopathic arthritis (oJIA) in the paediatric rheumatology department of Ankara City Hospital between April 2009 and September 2022. The relationship between small joint involvement and demographic, clinical, and laboratory findings and prognosis was investigated by statistical methods with the data recorded from the medical records of oJIA patients. Results: Of the 198 patients diagnosed with oJIA, small joint involvement was observed in a total of 20 (10%) patients, 11 (5.5%) at the time of diagnosis, and 9 (4.5%) during the follow-up period. The frequency of small joint involvement in extended oJIA was significantly higher than in persistent oJIA (P = .001). Patients with small joint involvement had significantly higher erythrocyte sedimentation rate and C-reactive protein values at admission (P = .047, P = .038) and Juvenile Arthritis Disease Activity Score at 3, 6, and 12 months (P = .001, P = .001, P = .018). The need for conventional disease-modifying antirheumatic drugs and biologic disease-modifying antirheumatic drugs was significantly higher in patients with small joint involvement (P = .001, P = .001). Conclusions: oJIA patients with small joint involvement may have higher acute phase reactants at diagnosis, a more extended course and active disease in follow-up, and the need for treatment escalation. [ABSTRACT FROM AUTHOR]

Objectives: To assess the link between the administration of biologic disease-modifying antirheumatic drugs (bDMARDs) and the risk of malignancy in human leukocyte antigen B27 (HLA-B27)-positive patients with ankylosing spondylitis (AS) experiencing sustained inflammation. Methods: Between 2006 and 2021, 1445 HLA-B27-positive patients with AS were retrospectively evaluated. Among them, 112 patients required bDMARD therapy. The study compared conventional therapy with bDMARDs and investigated the risk factors for developing malignancies. Results: During 8253 patient-years of follow-up, 38 (2.6%) patients developed various malignancies, including lung, liver, breast, and colon cancer. The risk of malignancy was significantly higher in the bDMARD-treated group compared to PS-matched groups receiving conventional synthetic DMARDs (csDMARD) and non-steroidal anti-inflammatory drugs. The cumulative risk of malignancies increased significantly after 6 years of follow-up. All patients who developed malignancy after bDMARD therapy received tumor necrosis factor-α inhibitors. Requiring bDMARD therapy, requiring bDMARDs in combination with csDMARD therapy, and being diagnosed with AS after 30 years of age were independent risk factors for developing malignancy. Conclusions: HLA-B27-positive AS patients with sustained inflammation requiring biologic therapy, particularly if diagnosed after age 30, may have an increased risk of malignancy. Regular cancer screenings are advisable for these patients while undergoing biologic treatment. [ABSTRACT FROM AUTHOR]

Objective: Our objective was to evaluate the association of serum biomarkers with baseline psoriatic arthritis (PsA) disease activity, pharmacodynamic effects of deucravacitinib on biomarker levels, and the relationship between biomarkers and clinical responses to deucravacitinib. Methods: The phase 2 trial (ClinicalTrials.gov identifier: NCT03881059) randomly assigned 203 patients with PsA 1:1:1 to placebo, deucravacitinib at 6 mg once daily (QD), or deucravacitinib at 12 mg QD. Serum biomarkers associated with the interleukin 23 (IL‐23) pathway (IL‐17A, β‐defensin [BD‐2], and IL‐19), type I interferon pathway, inflammation, and collagen matrix turnover were measured by immunoassay. Clinical responses (≥75% improvement from baseline in the Psoriasis Area and Severity Index [PASI75] and ≥20% improvement from baseline in American College of Rheumatology criteria [ACR20] responses) were measured at week 16. Hematologic variables were also assessed. Results: IL‐17A, BD‐2, and IL‐19 had a modest association with PASI scores (r = 0.4, r = 0.56, and r = 0.5, respectively) at baseline. In deucravacitinib groups, IL‐17A, BD‐2, IL‐19, C‐X‐C motif ligand 9 (CXCL9), CXCL10, C‐reactive protein, matrix metalloproteinase 3, and collagen type 4 degradation marker levels were significantly reduced at week 16 versus baseline (P < 0.01); higher levels of IL‐23 pathway–associated biomarkers predicted higher PASI75 and ACR20 response rates in deucravacitinib‐treated patients. Significantly higher PASI75 response rates were seen in patients with high baseline IL‐17A (odds ratio 15.76) and BD‐2 levels (odds ratio 15.41) versus low baseline IL‐17A and BD‐2 levels. Changes in hematologic variables that are characteristic of JAK inhibition were not observed with deucravacitinib. Conclusion: Deucravacitinib significantly impacted biomarkers associated with Tyk2 signaling pathways of key inflammatory cytokines, including IL‐23 and type I interferon, and those related to collagen matrix turnover. These biomarkers may predict treatment responses to deucravacitinib. [ABSTRACT FROM AUTHOR]

Objective: To compare the risk of gastrointestinal perforation (GIP), a rare but serious adverse event, in patients who a JAK inhibitor (JAKi; tofacitinib, baricitinib, upadacitinib, or filgotinib) versus adalimumab (tumor necrosis factor inhibitor) among a comprehensive real‐world population of patients with rheumatic diseases. Methods: We conducted a nationwide population‐based cohort study of the French national health data system, the exposed group that received a JAKi and the comparison group adalimumab. We included all individuals with a rheumatic disease who had their first dispensation of these treatments from July 2017 to December 2021. The primary endpoint was the occurrence of GIP (end of follow‐up May 2022). Weighted hazard ratios (wHRs) were estimated with the inverse probability of treatment weighting method to account for confounding factors. Concomitant administration of systemic glucocorticoids, nonsteroidal anti‐inflammatory drugs, and proton‐pump inhibitors were time‐varying variables. Results: The cohort included 39,758 patients: 12,335 and 27,423 in the groups that received a JAKi and adalimumab (mean age 58.2 and 47.3 years; female 76% and 58%; rheumatoid arthritis 85.3% and 27.3%, and psoriatic arthritis/axial spondyloarthritis 14.7% and 72.7%), respectively. During follow‐up, 38 and 42 GIPs occurred in the groups that received a JAKi and adalimumab groups; incidence rates were 2.1 (95% confidence interval [CI] 1.5–2.8) and 1.1 (95% CI 0.8–1.5) per 1,000 person‐years, respectively. Rates of GIP did not differ between the groups that received a JAKi and adalimumab: wHR 1.1 (95% CI 0.7–1.9; P = 0.65). Despite the lack of power in some subgroup analyses, results were consistent whatever the subgroup of a type of JAKi received or subgroup with a type of rheumatic disease. Conclusion: In this nationwide cohort study, the rates of GIPs did not differ between groups of patients who received JAKi and adalimumab treatment. These results need to be confirmed in other observational studies. [ABSTRACT FROM AUTHOR]

This document is a letter published in the journal Clinical Rheumatology. It discusses the use of methotrexate (MTX) and tumor necrosis factor inhibitors (TNFi) in patients with rheumatoid arthritis-associated interstitial lung disease (RA-ILD). The letter presents the results of a survey conducted among rheumatologists regarding their practices and opinions on the use of these medications in RA-ILD. The survey found that many rheumatologists would perform pulmonary screening prior to initiating MTX or TNFi, but most would not repeat screening. The majority of respondents would avoid MTX in patients with a documented history of ILD or hypersensitivity pneumonitis (HP). The letter also mentions the release of new guidelines by the American College of Rheumatology (ACR) for the management of systemic autoimmune rheumatic disease-associated ILD, which may impact clinical practice. The authors acknowledge the limitations of the survey and suggest further exploration of these practice trends in light of the new guidelines. [Extracted from the article]

Objectives: To evaluate the survival of different biologic or targeted-synthetic disease-modifying antirheumatic drugs (b/tsDMARD) administered after fulfilling difficult-to-treat rheumatoid arthritis (D2TRA) criteria, and to assess factors related to treatment discontinuation. Methods: Retrospective study including D2TRA patients. Drug retention of the b/tsDMARD administered after fulfilling D2TRA was assessed by Kaplan–Meier plots and the log-rank test. Cox hazard models were used to identify factors affecting treatment discontinuation. Results: Of the 122 patients included, 75 maintained active treatment (61.5%) with a subsequent line after D2T compared to 47 (38.5%) who discontinued and required more successive lines of b/tsDMARDs. The median survival of the treatments was 78.3(7.6) months and the treatment after D2T with the better rate of survival was rituximab, followed by JAKi and IL6Ri, while worse survival rates were associated with abatacept and TNFi. Significant differences were noted among b/tsDMARDs (log-rank p < 0.01) and to evaluate these differences, a Cox regression was performed, taking each b/tsDMARD as a reference and comparing it with the others. DAS28 values 6-months after initiation of treatment were higher in those patients who discontinued treatment [4.4(1.2) vs 3.5(1.3), p = 0.01]. The multivariate cox regression model revealed that treatment choice after D2T [HR = 1.26(95%CI 1.06–1.05)] and lower DAS28 values at 6 months [HR = 1.49(95%CI 1.16–1.52)] were independent risk factors associated with treatment discontinuation. Conclusions: Once patients met the D2TRA criteria, the subsequent line of b/tsDMARDs with the best survival rates were rituximab, JAKi and IL6Ri. Moreover, DAS28 at 6-months of treatment after D2T was an independent risk factor for drug discontinuation. Key Points • Rituximab, IL6Ri and JAKi have better retention rates in patients after fulfilling D2TRA criteria • Clinical disease activity in the first six months after fulfillment of D2TRA criteria is an independent risk factor of subsequent treatment survival [ABSTRACT FROM AUTHOR]

The article examines the relationship between biologic treatments for psoriasis and the risk of developing depression, based on a retrospective analysis of U.S. administrative claims data. Topics include the reduced incidence of depression among patients using biologics compared to conventional treatments, the relative risk reduction associated with different classes of biologics, and the implications of these findings for future treatment strategies.

Data on COVID-19 re-infections in patients with systemic rheumatic diseases (SRDs) are lacking. We aimed to describe the course and outcomes of COVID-19 re-infections in these patients versus controls. In this single-center retrospective study, we included 167 consecutive SRD patients with at least one COVID-19 re-infection (mean age 47.3 years, females 70.7%). SRD patients were compared in terms of patient-perceived COVID-19 re-infection severity and hospitalizations/deaths with 167 age/sex-matched non-SRD controls. Logistic regression analysis was performed to assess potential milder re-infection versus primary infection severity, adjusting for study group, demographics (age, sex), vaccination status, body mass index, smoking, and comorbidities. 23 and 7 out of 167 re-infected SRD patients experienced two and three re-infections, respectively, which were comparable to the re-infection rates in controls (two: 32; and three: 2) who also had comparable COVID-19 vaccination history (89% and 95% vaccinated, respectively). In the initial infection, patients with SRDs were hospitalized (7.2% versus 1.8%, p = 0.017), and had received antiviral treatment (16.1% versus 4.7%, p < 0.001) more frequently than controls. However, hospitalizations (1.8% vs 0.6%) and antiviral treatment (7.8% vs 3.5%) did not differ (p > 0.05) between patients and controls at the first re-infection, as well as during the second and third re-infection; no deaths were recorded. Perceived severity of re-infections was also comparable between patients and controls (p = 0.847) and among those on biologic DMARDs or not (p = 0.482). In multivariable analysis, neither SRDs presence nor demographics or comorbidities were associated with COVID-19 re-infection severity. COVID-19 re-infection severity (patient-perceived/hospitalizations/deaths) did not differ between SRDs and controls. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a worldwide public health problem. Interventions to delay or prevent the onset of RA have attracted much attention in recent years, and researchers are now exploring various prevention strategies. At present, there is still no unified consensus for RA prevention, but targeting therapeutic windows and implementing interventions for at-risk individuals are extremely important. Due to the limited number of clinical trials on pharmacologic interventions, further studies are needed to explore and establish optimal intervention regimens and effective measures to prevent progression to RA. In this review, we introduce the RA disease process and risk factors, and present research on the use of both Western and Chinese medicine from clinical perspectives regarding RA prevention. Furthermore, we describe several complete and ongoing clinical studies on the use of Chinese herbal formulae for the prevention of RA. [ABSTRACT FROM AUTHOR]

Objective. To analyze the long-term survival of subcutaneous biosimilar tumor necrosis factor inhibitors compared to the originator molecules in patients with rheumatic diseases, as well as the factors associated with drug discontinuation. Methods. Retrospective analysis of BIOBADASER, the Spanish multicenter prospective registry of patients with rheumatic disease receiving biologic and targeted disease-modifying antirheumatic drugs. Patients who started etanercept (ETN) or adalimumab (ADA) from January 2016 to October 2023 were included. The survival probabilities of biosimilars and originators were compared using Kaplan-Meier estimating curves. To identify factors associated with differences in the retention rates, hazard ratios (HR) were estimated using Cox regression models for all and specific causes (inefficacy or adverse events [AEs]) of discontinuation. Results. A total of 4162 patients received 4723 treatment courses (2991 courses of ADA and 1732 courses of ETN), of which 722 (15.29%) were with originator molecules and 4001 (84.71%) were with biosimilars. The originators were more frequently discontinued than biosimilars (53.32% vs 33.37%, respectively). The main reason for discontinuation was inefficacy (60.35% of the treatments). The risk of overall discontinuation was lower for biosimilars (adjusted HR 0.84, 95% CI 0.75-0.95). Female sex, obesity, and second or later treatment lines increased the risk of discontinuation, whereas disease duration and the use of concomitant methotrexate were associated with a greater survival. When assessing cause-specific reasons of discontinuation, excluding nonmedical switching, the results from the crude and adjusted analyses showed no significant differences in the retention rate between biosimilars and originators. Conclusion. No significant differences were found between treatments in long-term survival due to inefficacy or AEs. [ABSTRACT FROM AUTHOR]

Background: Difficult-to-treat Rheumatoid arthritis (D2T RA) is primarily characterised by failure of at least two different mechanism of action biologic/targeted synthetic disease-modifying antirheumatic drug (DMARDs) with evidence of active/progressive disease. While a variety of drugs have been used in previous studies to treat D2T RA, there has been no systematic summary of these drugs. This study conducted a systematic review of randomized controlled trials aimed at analyzing the efficacy and safety of individual therapeutic agents for the treatment of D2T RA and recommending the optimal therapeutic dose. Methods: The English databases were searched for studies on the treatment of D2T RA published between the date of the database's establishment and March, 2024. This study uses R 3.1.2 for data analysis, and the rjags package runs JAGS 3.4.0.20. The study fitted a stochastic effects Bayesian network meta-analysis for each outcome measure. Result: A total of 42 studies were included in this study. Compared with placebo, the improvement of Disease Activity Score of 28 Joints (DAS28) score is ranked from high to low as tocilizumab, baricitinib and opinercept. The improvement of American College of Rheumatology 50 response (ACR50) score in patients with drug use was ranked from good to poor as follows: olokizumab, tocilizumab, adalimumab, baricitinib, and upadacitinib, and 8 mg/4w tocilizumab demonstrated the best efficacy. Notably, rituximab is generally the safest drug. Janus kinase (JAK) inhibitors and T cell costimulation modulators are effective in D2T RA refractory to biologic DMARDs, while JAK inhibitors and interleukin-6 (IL-6) inhibitors show effectiveness in D2T RA refractory to csDMARDs. Conclusion: Tocilizumab and rituximab have better efficacy and safety in the treatment of D2T RA, and the 8 mg/4w dose of tocilizumab may be the first choice for achieving disease remission. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic immune-mediated inflammatory disease which can induce progressive disability if not properly treated early. Over the last 20 years, the improvement of knowledge on the pathogenesis of the disease has made available several drugs targeting key elements of the pathogenetic process, which now represent the preferred treatment option after the failure of first-line therapy with conventional drugs such as methotrexate (MTX). To this category of targeted drugs belong anti-cytokine or cell-targeted biological agents and more recently also Janus kinase inhibitors (JAKis). In the absence to date of specific biomarkers to guide the therapeutic choice in the context of true precision medicine, the choice of the first targeted drug after MTX failure is guided by treatment cost (especially after the marketing of biosimilar products) and by the clinical characteristics of the patient (age, sex, comorbidities and compliance) and the disease (presence or absence of autoantibodies and systemic or extra-articular manifestations), which may influence the efficacy and safety profile of the available products. This viewpoint focuses on the decision-making process underlying the personalized approach to RA therapy and will analyse the evidence in the literature supporting the choice of individual products and in particular the differential choice between biological drugs and JAKis. [ABSTRACT FROM AUTHOR]

Purpose: Despite efficient biological disease-modifying antirheumatic drugs (bDMARDs) Rheumatoid Arthritis (RA) patients still suffer from high fatigue. This study aims to further our knowledge by assessing severity levels of the various fatigue dimensions and their associations with pain, sleep quality, and psychological well-being in bDMARDs treated RA patients. Material and Methods: The sample consisted of 146 RA patients (84.9% females; mean age 56.6 ± 13.6 years), who completed the MFI-20, SF-36, PSQI, GAD-7 and PHQ-9. Correlation analyses and multiple linear regressions were used to analyse the data. Results: General fatigue was the highest reported type of fatigue, followed by physical fatigue dimensions. In the final regression model, pain and disability were significantly associated with physical fatigue (p ≤ 0.001, p ≤ 0.05, respectively) and reduced activity (p ≤ 0.01, p ≤ 0.05, respectively). Anxiety was significantly associated with mental fatigue (p ≤ 0.05) and reduced motivation (p ≤ 0.01). Regression analyses showed no significant associations between depression, sleep quality, and fatigue in any of the final models. Conclusions: Our findings indicate that effectively addressing fatigue in RA patients requires an individualized approach. This approach should acknowledge the varying degrees of fatigue across different fatigue dimensions (physical or mental), while also taking into account the patient's mental health problems, pain levels, and disability levels. IMPLICATIONS FOR REHABILITATION: despite the high prevalence of fatigue in rheumatoid arthritis (RA), the patients reported that 79% of healthcare professionals do not assess fatigue during visits; therefore, a measure of fatigue should be a part of routine medical examinations rehabilitation professionals should evaluate multidimensional fatigue, which seems to be more informative than a single measure of severity development and use of an effective individual non-pharmacological management program, based on an understanding of the variables associated with multidimensional fatigue may help in improving the quality of life of patients with RA [ABSTRACT FROM AUTHOR]

Background: To assess the association between various systemic lupus erythematosus (SLE) disease manifestations, SLE disease activity index 2000 (SLEDAI-2K), systemic lupus international collaborating clinics/American College of Rheumatology Damage Index (SLICC/ACR- SDI) and serum levels of Slit2 in SLE patients. Results: The mean age of SLE patients was 31.12 ± 8.68 years while the age at onset was 26.05 ± 7.60 years. Female: male was 9 vs 1. The mean serum levels of Slit2 in SLE patients were significantly higher than the controls (0.55 ± 0.25 vs 0.42 ± 0.15) (P = 0.013). There was no significant difference in Slit2 levels between patients with active vs inactive SLE (P = 0.353) or between patients with and without lupus nephritis (P = 0.900). An insignificant difference in Slit2 levels was found among SLE patients using SDI (P = 0.982). No significant correlations were observed between the serum Slit2 and SLE patients' demographics, laboratory data, SLEDAI-2K, and SDI except for a positive correlation with platelets and a negative correlation with serum albumin. ROC curve analysis showed that at a cutoff value of 0.44, the area under the curve was 0.677 (95% CI 0.538–0.816, P = 0.013) with a sensitivity of 74%, specificity of 56%, and accuracy of 68%. Conclusion: While we observed elevated serum Slit2 levels in SLE patients, there was no significant correlation observed between serum Slit2 levels and SLE clinical manifestations, disease activity, or damage index. Trial registration: NCT05105217. Registered 3 November 2021 [ABSTRACT FROM AUTHOR]

Introduction: With an increasing number of biologic/targeted synthetic disease-modifying antirheumatic drug options available for the treatment of active ankylosing spondylitis (AS), also known as radiographic axial spondyloarthritis, it is of clinical interest to determine the comparative efficacy of these advanced therapies among populations with differing prior advanced therapy exposure. This study aimed to assess the comparative efficacy of approved advanced therapies for AS in tumor necrosis factor inhibitor (TNFi)-naïve and, separately, in TNFi inadequate responder/intolerant (-IR) populations. Methods: A systematic literature review was conducted to identify randomized clinical trials for TNFis, interleukin-17A inhibitors, and Janus kinase inhibitors used as advanced therapies for active AS. Clinical efficacy was considered by the Ankylosing Spondylitis Disease Activity Score low disease activity (ASDAS LDA) criteria, defined as ASDAS score less than 2.1, among approved therapies. Comparative efficacy in the TNFi-naïve population was assessed utilizing network meta-analysis, while comparative efficacy in the TNFi-IR population was assessed utilizing matching-adjusted indirect comparison. Odds ratios were calculated, from which absolute rates and numbers needed to treat were calculated. Safety in the form of trial-reported and placebo-adjusted rates of discontinuation due to adverse events (AEs) was reviewed. Results: Among the TNFi-naïve population, the estimated ASDAS LDA rate between week 12 and 16 was highest for patients treated with upadacitinib (52.8%) and lowest for patients treated with placebo (11.6%). Among the TNFi-IR population, the estimated ASDAS LDA rate was 41.3% for patients treated with upadacitinib and 17.5% for patients treated with ixekizumab. The trial-reported and placebo-adjusted rates of discontinuation due to AEs were generally low across included advanced therapies. Conclusions: Relative to other assessed therapies, upadacitinib demonstrated greater clinical efficacy per ASDAS LDA in the treatment of active AS in both TNFi-naïve and TNFi-IR populations. Head-to-head and real-world data comparisons are warranted to both validate these findings and aid medical decision makers. [ABSTRACT FROM AUTHOR]

Introduction: Biologic therapies are licensed for both psoriasis (PsO) and psoriatic arthritis (PsA) with some electronic medical record data suggest that IL (Interleukin)-23 blockers might be more protective in PsA prevention than TNF blockers; however, the findings have been inconsistent. Higher Psoriasis Area and Severity Index (PASI) scores have also been linked to an increased PsA risk. To clarify these unresolved issues we investigated biologic agents, methotrexate, phototherapy, and topical therapy for PsA prevention in patients with psoriasis. Methods: This retrospective cohort study analyzed data from 58,671 patients with psoriasis from the Israeli Meuhedet Health Services Organization database was evaluated for incident PsA. Patients were categorized on the basis of treatment: group 1, topical therapy; group 2, phototherapy; group 3, conventional disease-modifying antirheumatic drugs (cDMARDs; methotrexate); group 4, biologic DMARDs which was also stratified according to biologic class. Results: The PsA incidence rate was lower in the biologic agents' group versus the methotrexate group (HR 0.46 [95% CI 0.35–0.62]). The incidence rates per 100 person-years varied across biologic treatment groups, with the anti‑IL‑12/23 or anti‑IL‑23p19 group at 4.57, the anti-IL-17 group at 4.35, and the TNF inhibitor group at 2.55. No differences were found between various biological agents in terms of preventing PsA. The phototherapy group exhibited a higher PsA development rate than the topical therapy group (HR 1.85 [95% CI 1.65–2.07]). Conclusion: Biological agents are more effective than methotrexate in reducing incident PsA in patients with psoriasis. This lower rate of PsA on topical therapy compared to phototherapy supports the importance of psoriasis severity as a risk factor. [ABSTRACT FROM AUTHOR]

Background: In psoriatic arthritis (PsA), musculoskeletal ultrasound is a complementary tool to physical examination, useful even in patients in remission to detect subclinical activity. Objectives: The objective of the study was to assess the ultrasound prevalence of active enthesitis and synovitis in patients who reached the therapeutic target. Methods: This cross-sectional study included patients with at least 6 months of therapy with a targeted synthetic or biological disease-modifying antirheumatic drug who were in treatment target (i.e., DAPSA < 14). Patients underwent bilateral clinical and ultrasound examination of the elbow lateral epicondyle, quadriceps insertion, distal patellar tendon insertion, and Achilles enthesis for assessing enthesitis, and hand and foot joints for assessing synovitis. Enthesitis and synovitis were considered active if the power Doppler signal showed at least a score of one. Results: The study included 51 PsA patients, women (52.9%), with an average age of 55 years. Although the patients were within the DAPSA treatment target, 21.6% had at least one painful enthesis at clinical examination, 19.6% had ultrasound evidence of at least one active enthesitis and 15.7% had ultrasound signs of at least one active synovitis. Conclusions: Among PsA patients thought to be within the therapeutic target, ultrasound detected a non-negligible percentage of active enthesitis and synovitis. [ABSTRACT FROM AUTHOR]

Objective: The ORAL Surveillance trial found a dose‐dependent increase in venous thromboembolism (VTE) and pulmonary embolism (PE) events with tofacitinib versus tumor necrosis factor inhibitors (TNFi). We aimed to assess VTE incidence over time and explore risk factors of VTE, including disease activity, in ORAL Surveillance. Methods: Patients with rheumatoid arthritis (RA) aged 50 years or older with at least one additional cardiovascular risk factor received tofacitinib 5 or 10 mg twice daily (BID) or TNFi. Post hoc, cumulative probabilities and incidence rates (patients with first events/100 patient‐years) by 6‐month intervals were estimated for adjudicated VTE, deep vein thrombosis, and PE. Cox regression models identified risk factors. Clinical Disease Activity Index leading up to the event was explored in patients with VTE. Results: Cumulative probabilities for VTE and PE were higher with tofacitinib 10 mg BID, but not 5 mg BID, versus TNFi. Incidence rates were consistent across 6‐month intervals within treatments. Across treatments, risk factors for VTE included prior VTE, body mass index greater than or equal to 35 kg/m2, older age, and history of chronic lung disease. At the time of the event, most patients with VTE had active disease as defined by Clinical Disease Activity Index. Conclusion: Incidences of VTE and PE were higher with tofacitinib (10 > 5 mg BID) versus TNFi and were generally consistent over time. Across treatments, VTE risk factors were aligned with previous studies in the general RA population. These data highlight the importance of assessing VTE risk factors, including age, body mass index, and VTE history, when considering initiation of tofacitinib or TNFi in patients with active RA. [ABSTRACT FROM AUTHOR]

Background: Numerous studies support a bidirectional association between rheumatoid arthritis (RA), a chronic autoimmune degenerative inflammatory joint disease, and periodontitis, a chronic inflammatory disease caused by the immune reaction to bacteria organized in biofilms. RA and periodontitis are both multifactorial chronic inflammatory diseases that share common modifiable and non‐modifiable risk factors. There is no cure for RA; treatment is based on lifestyle modifications and a variety of medications: nonsteroidal anti‐inflammatory drugs (NSAID), glucocorticoids, and disease‐modifying antirheumatic drugs (DMARDs, e.g., conventional synthetic DMARDs [csDMARDs]; biological DMARDs [bDMARD] and targeted synthetic DMARDs). There are molecular pathways of inflammation that are common to both RA and periodontitis. Thus, there is a potential effect of RA treatments on periodontitis. This systematic review aims to assess the impact of antirheumatic agents on periodontal conditions of patients suffering from both RA and periodontitis. Methods: PubMed/MEDLINE, Cochrane Library, and Embase online databases were systematically explored, and a manual search was performed to identify relevant studies published until January 2023. This review is registered in the PROSPERO database (CRD42023409006). Results: A total of 2827 articles were identified, and 35 fulfilled the inclusion criteria. The included studies generally show a consensus that, at normal dosage, NSAID and corticosteroids have negligible impact on periodontium. Similarly, csDMARD alone or in combination with other csDMARD demonstrated no adverse effect on periodontium. Monotherapy with bDMARD had a positive effect on periodontal pocket depths and gingival inflammation in the longitudinal studies up to 6 months but showed negligible effect on the periodontium in interventional studies with a longer follow‐up (9 months and 15.1 months). However, the combination of tumor necrosis factor (TNF)‐α inhibitors + methotrexate (MTX) was associated with a rise in gingival inflammation. Due to the considerable heterogeneity of the study designs, a meta‐analysis could not reasonably be performed. Conclusion: Within the limitations of the available studies, there is evidence to suggest that bDMARD monotherapy may improve the periodontal condition of RA patients with periodontal disease to a certain extent; the concomitant medication of TNF inhibitor + MTX could worsen gingival inflammation. More data are required to understand the impact of RA therapies on periodontal health. [ABSTRACT FROM AUTHOR]

Objective To investigate the risk of DM and evaluate the impact of SLE therapies on the risk of developing DM in patients with SLE. Methods Electronic database searches of PubMed, Embase, Cochrane Library and Web of Science were performed from inception to February 2023. Cohort and cross-sectional studies that analysed the risk of DM in patients with SLE were included. The associations between diabetes and antirheumatic agents, such as antimalarials and glucocorticoids, were analysed in cohort studies. Data were pooled using fixed- or random-effects meta-analysis to estimate pooled odd ratios (OR), relative risks (RR) and 95% confidence intervals (CIs). This study was registered with PROSPERO (CRD42023402774). Results A total of 37 studies (23 cross-sectional and 14 cohort studies) involving 266 537 patients with SLE were included. The pooled analyses from cross-sectional studies and cohort studies did not show an increased risk of DM in SLE patients (OR = 1.05, 95% CI 0.87–1.27; P  = 0.63 and RR = 1.32, 95% CI 0.93–1.87; P  = 0.12, respectively). However, several cohort studies consistently demonstrated a reduced risk of diabetes with antimalarials, while glucocorticoid use has been associated with an increased risk of developing diabetes. Age, sex, hypertension and immunosuppressants have not been identified as risk factors for DM in SLE patients. Conclusion Although there was no increased risk of DM in patients with SLE compared with controls, HCQ users or adherents had a decreased risk, whereas glucocorticoid users had an increased risk. [ABSTRACT FROM AUTHOR]

Objective To elucidate the differential effects of biological/target synthesized DMARDs (b/tsDMARDs) on bone metabolism in patients with rheumatoid arthritis (RA) in a real-world cohort. Methods This was a multicentre prospective observational study of RA patients enrolled at the time of first b/tsDMARDs administration. Bone mineral density (BMD) and bone turnover markers (BTMs) were measured during the 52-week observation. The study was designed to enrol all eligible RA patients. The end-points were differences in changes in BMD according to b/tsDMARD type, and the correlation between BMD and BTMs. Results A total of 1164 patients were enrolled in this study. b/tsDMARDs improved RA disease activity from mean CDAI 25.5 at baseline to 4.5 at week 26. Patients not receiving anti-osteoporotic agents (anti-OP) at baseline with no history of fracture experienced a significant decrease in both femoral neck (F: mean 0.666–0.655 g/cm3) and radial (R: 0.518–0.514) BMD at week 26. Despite maintaining low CDAI levels during weeks 26–52 (5.3–4.4), there was a continued decline in BMD (F: 0.653, R: 0.509. Weeks 52). None of the b/tsDMARDs type preserved BMD. Conversely, patients receiving anti-OP at baseline maintained stable BMD throughout the study (Weeks 0/26/52. F: 0.551/0.551/0.555, R: 0.415/0.416/0.415). Although BTMs were changed by b/tsDMARDs, the changes were unrelated to those in BMD. Conclusion Our study suggested the progression of osteoporosis in RA patients during b/tsDMARDs treatment without anti-OP. BTMs may not reflect BMD change. Regular monitoring of BMD in RA should be considered for early management of osteoporosis. [ABSTRACT FROM AUTHOR]

Objectives To investigate if disease activity among elderly RA patients >75 years of age has changed over time in the real-world clinical setting. Methods Data from an observational multicentre registry of RA patients in Japan were analysed. The primary outcome was to evaluate the changes in the proportion of very elderly RA patients (>75 years) who achieved remission and low disease activity (LDA), from 2014 to 2021. The secondary outcome was to identify factors associated with remission and LDA by comparing demographic and clinical characteristics among the patients who had a study visit within the study period, using multivariate logistic regression. Results A total of 32 161 patient visits were identified from 2014 to 2021. The proportion of patients >75 years of age increased from 16.5% to 26.9%, with biologics and targeted synthetic DMARDs (b/tsDMARDs) use increasing and glucocorticoids use decreasing, while conventional synthetic DMARDs use remained relatively stable. The proportion of RA patients >75 years of age achieving remission and LDA significantly increased from 62.2% to 78.2% (P for trend < 0.001). A negative factor associated with achieving remission and LDA was glucocorticoid use, seropositivity and a history of previous b/tsDMARDs use while MTX use was associated positively, independent of other predictors. Conclusions In our cohort, disease activity among very elderly RA patients has improved over time. The study suggests the importance of using a treat-to-target approach in very elderly RA patients to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Objective Caution has been advocated recently when using Janus kinase inhibitors (JAKi) in rheumatoid arthritis (RA) patients with an unfavourable cardiovascular risk profile. We aimed to compare the incidences in cardiovascular events between JAKi and biologic DMARDs (bDMARDs) in a large population of RA patients. Methods RA patients starting a new bDMARD or JAKi between 1 August 2018 and 31 January 2022 have been selected from IQVIA's Dutch Real-World Data Longitudinal Prescription database, covering about 63% of outpatient prescriptions in the Netherlands. Study outcome was a cardiovascular event, defined as the start of platelet aggregation inhibitors during the study period. The incidence densities of cardiovascular events were compared between JAKi and bDMARDs using multilevel Poisson regression, adjusted for exposure time and confounders. Results The number of unique patients included was 15 191, with 28 481 patient-years on treatment with either JAKi (2373) or bDMARDs (26 108). Most patients were female (72%) and median age was 62 years. We found 36 cardiovascular events (1.52 events/100 patient-years) during therapy with JAKi and 383 events (1.47 events/100 patient-years) during therapy with bDMARDs, resulting in an adjusted incidence rate ratio (IRR) of 0.99 for JAKi compared with bDMARDs (95% CI: 0.70, 1.41). Sub-analyses in patients >65 years, by sex, or separately for tofacitinib and baricitinib, yielded similar results. Conclusion In a large Dutch general RA population, the risk of cardiovascular events seems not to be different between JAKi users and those using bDMARDs, although a small increase in higher risk patients cannot be excluded. [ABSTRACT FROM AUTHOR]

Objective To determine whether persistent complete B cell (BC) depletion was associated with a better clinical response in rheumatoid arthritis (RA) patients long-term treated with rituximab (RTX). Methods We conducted a retrospective study including RA patients admitted for a new infusion between 2019 and 2021. The primary endpoint was the comparison of the mean disease activity score based on 28 joints (DAS28)-CRP at each of the four last infusion visits between patients with persistent complete BC depletion (mean CD19 counts <18/µl at each of the last four visits) or without persistent complete BC depletion (mean CD19 counts of the last four visits ≥18/µl). Secondary endpoints included DAS28, pain/fatigue visual analogue scale, CRP, gammaglobulins and the frequency of self-reported RA flares. Results Of the 126 patients in maintenance therapy with RTX [exposure period: 76 (5) months, 14 (7) infusions received], 43 (34%) had persistent complete BC depletion at each of the four last infusions. The mean DAS28-CRP calculated at each of the four last infusion visits did not significantly differ according to persistence or not of complete BC depletion. This result remained unchanged after adjusting for antibody status, number of previous therapies, number of RTX infusion and cumulative RTX dose. All secondary outcomes were also not significantly different between the two groups. Conclusion Maintaining complete BC depletion does not appear to be a therapeutic target to achieve in RA patients in long-term maintenance therapy with RTX. There is a limited benefit of monitoring CD19 in RA patients long-term treated with RTX and having achieved low disease activity/remission. [ABSTRACT FROM AUTHOR]

Biological disease-modifying antirheumatic drugs (bDMARD) have improved the clinical course and quality of life of patients with rheumatoid arthritis (RA). However, some patients failed to respond or have an insufficient response to bDMARD early in the course of the treatment. To determine the percentage of RA patients who need to switch due to ineffectiveness in the first year of treatment and to identify specific baseline features as possible predictors of switch due to ineffectiveness in the first year of treatment. An observational retrospective study was conducted with patients with RA that started their first bDMARD. Demographic data, disease characteristics, disease activity data scores, laboratory parameters and treatment at baseline were collected. The proportion of patients who failed to respond and who switched to another bDMARD in the first year of treatment was calculated. A total of 437 (364 females, 83.3%) patients with RA were included. The majority of these patients started an anti-TNF-α agent (n = 315, 72.1%). Forty-eight (11.0%) patients failed to respond to the bDMARD in the first year of treatment. There were significantly more current or former smokers (p = 0.030), with a history of depression (p = 0.003) and positive for RF at baseline (p = 0.014) in the switch group. In the multivariate analysis, anti-TNF-α agents use (OR 8.3, 95% CI 2.4–28.8, p = 0.001), tobacco exposure (OR 2.3, 95% CI 1.1–4.8, p = 0.02) and history of depression (OR 3.1, 95% CI 1.3–7.7) seem to predict the need to switch in the first year of treatment due to ineffectiveness. In our study, tobacco exposure and depression appear to be modifiable risk factors associated with early switching due to ineffectiveness. Addressing these factors in daily clinical practice is crucial to enhance the overall response to therapy and improve the well-being of patients. [ABSTRACT FROM AUTHOR]

This letter to the editor discusses a comparative study that examined the differences between paradoxical psoriasis (PP) and classical psoriasis. The study found that PP patients had a higher frequency of accompanying autoimmune/inflammatory diseases and were exposed to a higher number of biological agents. Additionally, PP patients had less frequent trunk and extremity involvement compared to classical psoriasis patients. The study suggests that PP patients may require different treatment approaches due to these differences. Another finding of the study was that PP patients had lower need for biological treatment and faster response times to treatment compared to classical psoriasis patients. The study suggests that these differences may be due to variations in the underlying causes of PP and classical psoriasis. The study emphasizes the importance of considering concurrent autoimmune/inflammatory diseases and previous use of biologics when making treatment decisions for PP. [Extracted from the article]

This study provides a detailed understanding of the preclinical pharmacokinetics and metabolism of ELP‐004, an osteoclast inhibitor in development for the treatment of bone erosion. Current treatments for arthritis, including biological disease‐modifying antirheumatic drugs, are not well‐tolerated in a substantial subset of arthritis patients and are expensive; therefore, new treatments are needed. Pharmacokinetic parameters of ELP‐004 were tested with intravenous, oral, and subcutaneous administration and found to be rapidly absorbed and distributed. We found that ELP‐004 was non‐mutagenic, did not induce chromosome aberrations, non‐cardiotoxic, and had minimal off‐target effects. Using in vitro hepatic systems, we found that ELP‐004 is primarily metabolized by CYP1A2 and CYP2B6 and predicted metabolic pathways were identified. Finally, we show that ELP‐004 inhibits osteoclast differentiation without suppressing overall T‐cell function. These preclinical data will inform future development of an oral compound as well as in vivo efficacy studies in mice. [ABSTRACT FROM AUTHOR]

The short-term use of glucocorticoids (GCs) in combination with methotrexate was recommended for the initial treatment of rheumatoid arthritis by the European League Against Rheumatism. A randomized controlled trial (GLORIA) showed that treatment of older patients with low-dose GCs in combination with disease-modifying anti-rheumatic drugs was more efficacious than disease-modifying anti-rheumatic drugs plus placebo in terms of disease activity control and prevention of joint destruction. Glucocorticoid-related adverse events were likely to increase relative to placebo, with no increase in serious adverse events and fractures over 2 years. Observational studies showed an increased risk of serious infections, cardiovascular events, and fractures associated with long-term continuation of GCs in older patients, but the adverse events may be associated not only with GC toxicity but also with poor disease control of rheumatoid arthritis. In the GLORIA study, low-dose GCs during 2 years could be tapered off safely, but many patients had a flare of disease activity after discontinuation of GCs. In the two representative large Japanese registries (IORRA and NinJa), the proportion of patients using GCs and non-tumor necrosis factor inhibitors increased with increasing age at disease onset, with a decreasing trend in methotrexate use. The proportion of patients in remission with GC treatment also increased with increasing age at onset. These suggested that it is not easy to discontinue GCs in older patients. If GCs cannot be terminated in the short term, it may be acceptable to use GCs to control disease activity for up to 2 years. [ABSTRACT FROM AUTHOR]

Background: While the variety of biologics (b) and targeted synthetic (ts) disease-modifying anti-rheumatic drugs (DMARDs) available for patients with psoriatic arthritis (PsA) has proved to be efficacious in randomized clinical trials, there is a growing importance to understand the benefits and potential drawbacks of these different therapies in real-world settings, which includes bio-experienced and older patients as well. Objective: To evaluate the real-world adherence, drug survival, and discontinuation risk of bDMARDs and tsDMARDs among patients with PsA, comprising both younger and older patients. Methods: A retrospective study using a computerized database. Treatment-naïve and treatment-experiencedpatients with PsA, younger and older than 60 years, who initiated treatment with bDMARDs [TNF-α inhibitors (TNF-αis), IL-17 inhibitors (IL-17is), IL-12/23 inhibitors (IL-12/23i)] or tsDMARDs (the PDE-4 inhibitor apremilast) during 2015–2018 were included. Adherence was assessed using the proportion of days covered (PDC) method. Time to discontinuation was analyzed using Kaplan–Meier estimates. Risk of discontinuation was estimated by Cox proportional hazard model. Results: We identified 427 eligible patients (22.2 % were older than 60 years), utilizing 673 treatment lines. The proportion of adherent patients (PDC ≥ 0.8) was similar (62.1–66.5%) across all lines of therapy and across different biologics (70.0–72.0%), while apremilast showed the lowest, in both treatment-naïve and experienced settings (43.6% and 25.5%, respectively). The Kaplan–Meier analysis showed that in the treatment-naïve TNF-αis had higher drug survival compared with apremilast (P = 0.032). Apremilast also had the lowest drug survival in the treatment-experienced group (P < 0.0001). Kaplan–Meier analysis by age groups showed similar drug survival rates in older (≥ 60 years) and younger (age < 60 years) patients, regardless of treatment-experience status. The multivariable model showed that apremilast had increased risk for discontinuation compared with TNF-αis. Conclusion: Adherence, drug survival and risk for discontinuation were similar for all included bDMARDs, regardless of treatment experience status, while apremilast showed lower rates and increased risk. Adherence and discontinuation rate were similar in older and younger patients. With the variety of drug modes of action available for patients with PsA, these findings may assist caregivers in selecting the appropriate treatment. [ABSTRACT FROM AUTHOR]

Biological disease-modifying antirheumatic drugs (bDMARDs) can have different effects on various clinical manifestations of ankylosing spondylitis (AS). Data on the effects of interleukin 17 inhibitors (IL17-i) on uveitis in AS continue to accumulate. Objective: to evaluate the effect of IL17-i therapy on the course of uveitis in AS. The study involved 73 patients with AS (New York criteria, 1984), who received IL17-i (57—secukinumab (SEC), 22—netakimab (NTK)) for at least 1 year. The average age of patients at the time of inclusion in the study was 41.93 ± 8.95 years, the average duration of AS was 10.75 ± 6.22 years. There were 40 men (56.7%) and 33 women (43.3%) among the patients. HLA-B27 was detected in 62/73 (85%), coxitis in 58 (79%), enthesitis in 63 (86.3%), peripheral arthritis in 57 (78%), psoriasis in 7 (9.5%), and inflammatory bowel disease (IBD) in 3 (4.1%) patients; in 6 (8.2%) patients, the disease started before the age of 16; 19 (26%) patients had at least one episode of uveitis during the course of the disease. The rates of uveitis was estimated by comparing the number of incidences per 100 patient-years before the start of bDMARDs therapy and during IL17-i using. The incidence rate of uveitis before the start of bDMARDs therapy for all patients was 8.3 per 100 pt-years (95% CI 0.065–0.107), during IL17-i therapy— 9.2 per 100 pt-years (95% CI 0.06–0.15), p = 0.72. The incidence rate of uveitis among patients who used SEC was 10.1 per 100 pt-years (95% CI 0.079–0.13) before the start of bDMARDs therapy and 9.4 per 100 pt-years (95% CI 0.05-0.15), p = 0.74 during SEC therapy. The incidence rate of uveitis among patients who used NTK was 4.8 per 100 pt-years (95% CI 0.028–0.08) before the start of bDMARDs therapy and 7.1 per 100 pt-years (95% CI 0.019–022), p = 0.3 during the NTK therapy. For patients with a history of uveitis, the incidence rate of uveitis was 22.5 per 100 pt-years (95% CI 0.18–0.28) before the start of therapy with bDMARDs and 29.1 per 100 pt-years (95% CI 0.18–0.43), p = 0.29 during IL17-i therapy. Occurrences of uveitis were observed in 4 of 57 patients (7%) during SEC therapy and in 1 of 25 (4%) patients during the NTK therapy. One case of new-onset uveitis was recorded during the using of SEC. There were no significant differences in the incidence rates of uveitis during IL17-i therapy compared with non-biological therapy. IL17-i therapy have not demonstrated a significant effect on the course of uveitis in AS in the study group. [ABSTRACT FROM AUTHOR]

Individuals diagnosed with ankylosing spondylitis (AS) face an increased risk of spine fractures, specifically cervical spine fractures (CS-Fxs). In the past two decades, biological disease-modifying antirheumatic drugs (bDMARDs) have provided considerable relief from pain and an enhanced sense of wellbeing for a large segment of AS patients. Despite these improvements, it remains unclear whether extended use of bDMARDs can indeed reduce the risk of spine fractures. In this study, we aimed to investigate the evolving patterns and epidemiology of traumatic CS-Fxs in both AS and non-AS populations. We hypothesized that the risk of CS-Fxs among AS patients would show a decreasing trend over time, while the risk among non-AS patients would remain constant. Retrospective cohort study based on a prospective database. A total of 3,598 consecutive patients with CS-Fxs were treated at Oslo University Hospital over an 8-year period. CS-Fxs in AS patients were contrasted with non-AS-related CS-Fxs in terms of temporal trends, age, sex, injury mechanism, associated cervical spinal cord injury (cSCI), need for surgical fixation, and 30-day mortality. Data regarding all CS-Fxs diagnosed between 2015 and 2022 were extracted from the Southeast Norway population-based quality control database for traumatic CS-Fxs. Categorical data were summarized using frequencies, and continuous data were summarized using medians. The Wilcoxon rank-sum test was used to compare continuous variables, and the chi-squared test and Fischer exact test were used to compare categorical variables. To investigate the trend in the incidence of fractures, two different Poisson models were fitted with the number of non-AS and AS fractures as dependent variables and the year as the explanatory variable. Over an 8-year period, we registered 3,622 CS-Fxs in 3598 patients, with AS patients accounting for 125 of these fractures. Relative to their non-AS counterparts, AS patients presented a 9-fold and 8-fold higher risk of initial and subsequent CS-Fxs, respectively. We observed a declining trend in AS-related CS-Fxs with an annual linear decrease of 8.4% (p=.026), whereas non-AS-related CS-Fxs showed an annual linear increase of 3.7% (p<.001). AS patients sustaining CS-Fxs were typically older (median age 70 vs 63 years), predominantly male (89% vs 67%), and more frequently experienced injuries due to falls (82% vs 57%). They also exhibited a higher prevalence of subaxial CS-Fxs (91% vs 62%), fewer C0-C2 CS-Fxs (14% vs 44%), a higher rate of associated cSCI (21% vs 11%), and a greater tendency for surgical fixation (66% vs 21%). We observed a 30-day mortality rate of 11% in AS patients and 5.4% in non-AS patients (p=.005). The results of this study confirm the elevated risk of CS-Fxs among AS patients, although this risk appears to show a decreasing trend. The most plausible explanation for this risk reduction is the widespread application of bDMARDs [ABSTRACT FROM AUTHOR]

Objective: We evaluated sex differences in time to initiation of receiving nonsteroidal anti‐inflammatory drugs (NSAIDs) or biologic disease‐modifying antirheumatic drugs (bDMARDs) among patients with axial spondyloarthritis (axSpA). Methods: Using the 2013 to 2018 IBM MarketScan Database, we identified 174,632 patients with axSpA aged ≥18 years. We evaluated the time between axSpA diagnosis and the first prescription NSAID dispensing (among those with no baseline NSAIDs reception) or bDMARDs infusion/procedure claim (among those who were dispensed two or more different prescription NSAIDs in the baseline period). Adjusted hazard ratios (aHRs) for time to initiation of patients receiving NSAIDs or bDMARDs were computed using survival analyses. Cox proportional hazard models estimated associations between sex and predictors of treatment initiation. Results: Average age at diagnosis was 48.2 years, 65.7% were female, and 37.8% were dispensed one or more NSAIDs before axSpA diagnosis. Of those who did not receive two or more different prescription NSAIDs before diagnosis, NSAID reception was initiated earlier in female patients than in male patients (NSAID reception initiators: female patients (32.9%), male patients (29.3%); aHR 1.14, 95% confidence interval [CI] 1.11–1.16). Among those who received two or more different prescription NSAIDs in the baseline period, 4.2% received a bDMARD, whereas 77.9% continued receiving NSAIDs after diagnosis. Time to bDMARD reception initiation was longer for female patients than for male patients (aHR 0.61, 95% CI 0.52–0.72), but bDMARDs were received sooner among those who received NSAIDs in the baseline period. Conclusion: Prescription NSAID reception was more common than initiation of receiving bDMARDs among patients newly diagnosed with axSpA. Female patients appeared more likely to continue receiving NSAIDs after diagnosis, and the time to initiation of receiving bDMARDs was longer for female patients than for male patients. [ABSTRACT FROM AUTHOR]

Objective. To describe the clinical features of patients with congenital heart disease (CHD) who subsequently developed systemic juvenile idiopathic arthritis (sJIA). Methods. We conducted a retrospective review of patients diagnosed with CHD and sJIA at our institution. Detailed clinical, laboratory, and radiographic data were collected from the medical record and reviewed with each patient's primary medical team. Results. Five patients with sJIA and CHD were identified. Each child had a unique cardiac anatomy, but all the patients required surgical repair during the first year of life. Four children had thymectomies at the time of cardiac surgery. Classic signs of sJIA such as fever (n = 5), rash (n = 5), and arthritis (n = 4) developed after surgical intervention in all the patients. The individuals in this cohort displayed risk factors associated with severe sJIA, including disease onset before 2 years of age (n = 5), elevated interleukin 18 levels (n = 5), baseline eosinophilia prior to initiation of biologic disease-modifying antirheumatic drugs (n = 4), and positivity for HLA-DRB1*15:01 alleles (n = 4). Macrophage activation syndrome (MAS) occurred in 3 patients and sJIA-associated lung disease (sJIA-LD) was identified in 4 patients. Two children died from complications of their cardiac and/or pulmonary disease. Conclusion. We identified an association between CHD and severe forms of sJIA. Although these findings will need to be confirmed in larger, multicenter cohorts, the results highlight the importance of considering a diagnosis of sJIA in children with CHD and remaining vigilant for complications such as MAS and sJIA-LD. [ABSTRACT FROM AUTHOR]

Objectives: This study aims to evaluate in a real-life Italian multicenter cohort of axial spondyloarthritis (axSpA) (1) the 4-year effectiveness and safety of secukinumab, (2) the drug retention rate (DRR), and (3) the impact of the line of bDMARDs treatment, subtype of axSpA, and sex on achieving low disease activity (LDA) and very low disease activity (VLDA). Methods: Consecutive axSpA patients receiving secukinumab between 2016 and 2023 were prospectively evaluated. Data on disease characteristics, previous/ongoing treatments, comorbidities, and follow-up duration were collected. Treatment response was evaluated at 6 and 12 months after initiation and yearly up to 48 months (T48). DRR and effectiveness outcomes were evaluated according to bDMARDs treatment, axSpA subtype, and sex. Infections and adverse events (AEs) were recorded. Results: We enrolled 272 patients (48.2% male; median age, 51; 39.7% HLA-B27+; 40.4% nr-axSpA), of whom 30.9% were naïve to secukinumab. Overall, secukinumab yielded improvement in effectiveness outcomes; the naïve patients maintained lower disease activity vs. the non-naïve ones. At T48, the LDA and VLDA rates were higher in naïve patients and in male individuals. Treatment was discontinued in 104 patients due to primary/secondary loss of effectiveness and in 34 patients due to AEs. The DRR at T48 was 67.4% in the whole population, regardless of treatment line, axSpA subtype, and sex. Conclusions: Secukinumab was safe and effective in all axSpA patients irrespective of treatment line, disease subtype, and sex. The patients achieved sustained 4-year remission and DRR. [ABSTRACT FROM AUTHOR]

Relapsing polychondritis (RP) is a systemic immune mediated disease characterized by recurrent episodes of inflammation in various cartilage-rich areas. RP may cause extensive tissue destruction and is associated with significant morbidity and mortality. In this multicenter study, we considered the remission status and long-term outcomes of RP in patients who were followed-up in six referral rheumatology centers in Iran. Outcomes of disease was assessed by remission status and RP induced damage. A total of 29 patients with RP were examined for enrollment in the study, and 26 patients with a minimum follow-up period of 6 months were included in the RP outcome analysis. Median time to control of symptoms and sustained remission were 5 and 23 weeks, respectively. Prednisolone was discontinued in 8 (30.8%) patients and medication-free remission was achieved in 7 (23.1%) patients. Regarding the disease course, 34.6% of patients had a relapsing–remitting course, 42.3% had a monophasic course, and 23.1% had an always-active course. Despite extensive treatment with immunosuppressive medications, RP induced damage was developed in 21 (80.8%) patients. Ear deformity and osteoporosis were the most common RP induced damage. Long-term remission and medications-free remission in RP is accessible. However, RP related damage occur in majority of patients. [ABSTRACT FROM AUTHOR]

Objective: To clarify the therapy response in orbital inflammatory diseases (OID), we analyzed the treatment effects of steroid therapy, the use of disease-modifying antirheumatic drugs (DMARDS), and biologicals in our tertiary referral center cohort. Methods: We collected the clinical and demographic data of all patients treated for non-specific orbital inflammation (NSOI) (n = 111) and IgG4-ROD (n = 13), respectively at our center from 2008 to 2020 and analyzed them with descriptive statistics. NSOI were sub-grouped according to the location into either idiopathic dacryoadenitis (DAs) (n = 78) or typical idiopathic orbital myositis (n = 32). Results: Mean age at first clinical manifestation was significantly different between subgroups (IOI: 49.5 ± 18, IgG4-ROD: 63.2 ± 14, p = 0.0171). Among all examined OID, 63 patients (50%) achieved full remission (FR) with corticosteroids (NSOI 53%/IgG4-ROD 31%). In contrast, classic myositis showed a significantly higher response (76%). Disease-modifying drugs (DMARDS) for myositis accomplished only 33% FR (NSOI 57%) and 66% did not respond sufficiently (NSOI 43%). The biologic agent (Rituximab) was significantly more efficient: 19 of 23 patients (82%) achieved full remission and only 4 (17%) did not respond fully and needed orbital irradiation or orbital decompressive surgery. [ABSTRACT FROM AUTHOR]

Reactive arthritis(ReA), a form of arthritis occurring post-infection, manifests with antecedent infection symptoms, arthritis, and extra-articular manifestations, categorizing it as spondyloarthritis. "Keratoderma blennorrhagicum" (characterized by pustular hyperkeratosis on palms and soles, resembling pustular psoriasis) represents the most typical skin manifestation of ReA, occurring in acute or chronic phases. Severe lesions necessitate systemic disease modifying antirheumatic drugs (DMARDs) or biologic therapies. This article reports a case of ReA with sacroiliitis and widespread pustular eruptions following a urinary tract infection. Treatment with sulfasalazine and thalidomide significantly improved sacroiliitis, but the skin rash remained persistent and recurring. Subsequent use of adalimumab and secukinumab resulted in worsening skin rash, prompting a switch to tofacitinib, leading to a remarkable improvement in pustular eruptions after 20 days of treatment. This case demonstrates successful application of tofacitinib in treating severe keratoderma blennorrhagicum refractory to conventional DMARDs and biologics, offering insights into JAK inhibition for challenging rheumatic diseases with skin involvement. [ABSTRACT FROM AUTHOR]